APPLICANT'S ABSTRACT: We have observed increased cerebrospinal fluid (CSF) and reduced grey and white matter volumes in many regions of the brains of chronic alcoholic men shortly after withdrawal. Over the first 4 weeks of abstinence, there is some reversibility of the CSF volume increase, especially ventricular enlargement. The brain shrinkage associated with chronic alcoholism accelerates with advancing age, and it is also associated with some measures of lifetime alcohol exposure, suggesting that the aging brain may be especially susceptible to the neurotoxic effects of alcohol. We have begun a longitudinal magnetic resonance imaging (MRI) study of morphological brain changes associated with chronic alcoholism in men. We will expand this study to include alcoholic and control women. We propose to add additional older male subjects, with early and late onset of alcoholism. We will follow all subjects over more extended periods of time in order to identify factors influencing the appearance, progression, and/or reversibility of neuroanatomic alterations. In addition we will explore the significance of the morphologic brain alterations in terms of neuropsychological (NP) and electrophysiology (ERP) function. The experimental design and subject selection are constructed to allow us to test the "vulnerable aging brain" vs the "cumulative alcohol toxicity" hypotheses regarding the aging/alcoholism interaction effect on brain morphology. NP testing will include assessment of neuroanatomically localized cognitive and motor functions. Scalp recorded ERP components, particularly the P3, will be analyzed using a newly developed statistical inverse solution, based on a 4-shell model of the brain. This analysis will allow us to differentiate between abnormalities attributable to changes in potential sources themselves and those attributable to non-brain (i.e., skull and scalp thickness) and brain (i.e., tissue reduction and CSF expansion) factors. Newly developed MRI acquisition sequences and analysis procedures will be used to enable quantitative assessments of specific neuroanatomic structures and production of whole section proton longitudinal relaxation time (T1) maps.